Oxidation of compounds metabolized through folate coenzyme pathways in vitamin B12-deficient rats

The effects of vitamin B₁₂ deficiency in rats and dietary supplementation with vitamin B₁₂ and/or l-methionine plus folate on the oxidation of compounds metabolized through folate coenzyme pathways were investigated. Rats fed a vitamin B₁₂-deficient diet oxidized significantly lower amounts in 60 min of l-histidine, glycine, sarcosine, formate, and l-serine to CO₂ than vitamin B₁₂-supplemented controls. Supplementation of the deficient diet with l-methionine plus folate restored the ability to oxidize the ring-2-carbon of l-histidine, the methyl group of sarcosine, and formate to the same level as that observed in animals receiving vitamin B₁₂. In contrast, oxidation of the 1-carbon of glycine and the 3-carbon of l-serine was not restored to control levels by addition of methionine plus folate to the vitamin B₁₂-deficient diet. Inhibition of the metabolism of the 2-carbon of glycine to CO₂ was partially overcome by additional dietary methionine and folate. Glycine synthase activity in homogenates paralleled the in vivo pattern of oxidation of the 1-carbon of glycine to CO₂, whereas sarcosine dehydrogenase activity appeared to increase 2-fold in vitamin B₁₂ deficiency.     

Cortactin Controls Surface Expression of the Voltage-gated Potassium Channel KV10.1

K_V10.1 is a voltage-gated potassium channel aberrantly expressed in many cases of cancer, and participates in cancer initiation and tumor progression. Its action as an oncoprotein can be inhibited by a functional monoclonal antibody, indicating a role for channels located at the plasma membrane, accessible to the antibody. Cortactin is an actin-interacting protein implicated in cytoskeletal architecture and often amplified in several types of cancer. In this study, we describe a physical and functional interaction between cortactin and K_V10.1. Binding of these two proteins occurs between the C terminus of K_V10.1 and the proline-rich domain of cortactin, regions targeted by many post-translational modifications. This interaction is specific for K_V10.1 and does not occur with K_V10.2. Cortactin controls the abundance of K_V10.1 at the plasma membrane and is required for functional expression of K_V10.1 channels.     

Plasma catecholamines: Arterial-venous differences and the influence of body temperature

Using sensitive radio-enzymatic assays, levels of plasma total catecholamines and norepinephrine in rats change dramatically with changes in body temperature. The decrease in plasma catecholamines induced by warming the animal is reflected in an apparent arterio-venous difference when arterial blood is obtained at room temperature and tail sampling is aided by heat induced vasodilation. Combined blockade of extraneuronal and neuronal uptake reduces this arterio-venous difference. Blood samples obtained from the decapitated trunk of the rat contain similar levels of plasma catecholamines as those obtained from indwelling carotid catheters. Blood levels of dopamine-betahydroxylase were similar whether obtained by venous sampling during heat-induced vasodilation, decapitation or indwelling arterial cannula.     

The protection against gentamicin nephrotoxicity in the streptozotocin-induced diabetic rat is not related to gender.

Since gender can influence the renal toxicity of a drug in a given species, the present study was undertaken to evaluate the role of sex in the protection against gentamicin (G)-induced nephrotoxicity afforded by diabetes mellitus (DM) in the rat. We have compared the effects of administration of G (40 mg/kg/day, for 14 days) on male and female DM Sprague-Dawley rats. Non-diabetic animals of both sexes receiving identical doses of G served as controls. At the end of the experiment on day 14, both female (F) and male (M) control groups had similar and marked evidence of nephrotoxicity: elevation of plasma creatinine (F 1.7 +/- 0.7; M 2.8 +/- 0.6 mg/dl), decrease in endogenous 24-h creatinine clearance (Ccr) (F0.3 +/- 0.1; M 0.2 +/- 0.1 ml/min/100 g BW), and histological evidence of severe acute tubular necrosis. In marked contrast, the DM rats showed no functional or morphological evidence of renal damage throughout the study regardless of their gender (day 14: plasma creatinine: F 0.2 +/- 0.03; M 0.2 +/- 0.02; Ccr: F 1.2 +/- 0.1; M 1.6 +/- 0.1 ml/min/100 g BW), and they also accumulated less G in their kidney cortex than the C rats. The male controls exhibited higher renal cortex accumulation of G than the female controls (p < 0.05), whereas the opposite occurred in the DM groups (p < 0.01). Because the validity of using Ccr for the evaluation of GFR changes in experimental nephrotoxicity has been questioned, we have compared, in a separate experiment, three different methods of estimation of GFR (simultaneous short clearances of inulin and Ccr, and 24-h Ccr) in conscious female Sprague-Dawley rats undergoing the same treatment with G described above. At no time during the study did the method used for estimation of the GFR influence the results. We conclude that male and female Sprague-Dawley rats with diabetes are functionally and morphologically equally protected against G. Furthermore, no gender-related differences in the magnitude of G-induced nephrotoxicity was demonstrated in the non-diabetic control animals.     

Genetic analysis of mitomycin C-induced interchange in Drosophila melanogaster females

A genetic analysis of an array of mitomycin-induced rearrangements in immature Drosophila oocytes is reported. Induced aberrations were recovered representing detachments of the compound-X chromosome, Y chromosome fragments, X chromosome loss and mosaicism. The spectrum of rearrangements induced by mitomycin C was very similar to that induced by X-ray treatment of immature oocytes. This work suggests that mitomycin C has two modes of action. The drug is radiomimetic for it induces the types of aberrations recovered after X-irradiation. Mitomycin C also seems to have a delayed effect which is reflected in the relatively high recovery of mosaics.     

Increasing picocyanobacteria success in shelf waters contributes to long‐term food web degradation

Continental margins are disproportionally important for global primary production, fisheries and CO₂ uptake. However, across the Northeast Atlantic shelves, there has been an ongoing summertime decline of key biota—large diatoms, dinoflagellates and copepods—that traditionally fuel higher tropic levels such as fish, sea birds and marine mammals. Here, we combine multiple time series with in situ process studies to link these declines to summer nutrient stress and increasing proportions of picophytoplankton that can comprise up to 90% of the combined pico‐ and nanophytoplankton biomass in coastal areas. Among the pico‐fraction, it is the cyanobacterium Synechococcus that flourishes when iron and nitrogen resupply to surface waters are diminished. Our field data show how traits beyond small size give Synechococcus a competitive edge over pico‐ and nanoeukaryotes. Key is their ability to grow at low irradiances near the nutricline, which is aided by their superior light‐harvesting system and high affinity to iron. However, minute size and lack of essential biomolecules (e.g. omega‐3 polyunsaturated fatty acids and sterols) render Synechococcus poor primary producers to sustain shelf sea food webs efficiently. The combination of earlier spring blooms and lower summer food quantity and quality creates an increasing period of suboptimal feeding conditions for zooplankton at a time of year when their metabolic demand is highest. We suggest that this nutrition‐related mismatch has contributed to the widespread, ~50% decline in summer copepod abundance we observe over the last 60 years. With Synechococcus clades being prominent from the tropics to the Arctic and their abundances increasing worldwide, our study informs projections of future food web dynamics in coastal and shelf areas where droughts and stratification lead to increasing nutrient starvation of surface waters.